rs12447690

Variant names:

• chr16-88264518-C-T
• rs12447690
• XM_047435026.1:c.-468G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047435026.1(LOC124900374):​c.-468G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 145,808 control chromosomes in the GnomAD database, including 22,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22729 hom., cov: 21)
• Consequence: LOC124900374 XM_047435026.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 42 publications found

Genes affected

LOC124900374 (HGNC:):

LINC02182 (HGNC:53044): (long intergenic non-protein coding RNA 2182)

ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

ZNF469 Gene-Disease associations (from GenCC):

• brittle cornea syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
• brittle cornea syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• aortic disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563190.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC107984862	NR_171662.1		n.274+343G>A		intron	N/A
	LOC107984862	NR_171663.1		n.370+247G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02182	ENST00000563190.1	TSL:3	n.120-11956C>T		intron	N/A
	LINC02182	ENST00000718466.1		n.140-11956C>T		intron	N/A
	LINC02182	ENST00000767800.1		n.144-11956C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.534 AC: 77792 AN: 145690 Hom.: 22712 Cov.: 21

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.534 AC: 77828 AN: 145808 Hom.: 22729 Cov.: 21 AF XY: 0.532 AC XY: 37633 AN XY: 70690

African (AFR) AF: 0.278 AC: 11008 AN: 39606

American (AMR) AF: 0.635 AC: 9213 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1789 AN: 3428

East Asian (EAS) AF: 0.751 AC: 3542 AN: 4716

South Asian (SAS) AF: 0.552 AC: 2437 AN: 4414

European-Finnish (FIN) AF: 0.575 AC: 5600 AN: 9738

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 42423 AN: 66220

Other (OTH) AF: 0.580 AC: 1150 AN: 1982

Alfa AF: 0.614 Hom.: 106282

Bravo AF: 0.533

Asia WGS AF: 0.610 AC: 2112 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.21
PhyloP100		0.055

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12447690; hg19: chr16-88298124;